It is often desirable to coat tablets of pharmaceutical products with a material which prohibits release of the active ingredient in the low pH medium of the stomach but enables rapid release in the higher pH medium of the upper small intestine. Such coatings are commonly referred to as enteric coatings. They are useful in protecting the active ingredient in the formulation from hydrolysis or degradation in the stomach and in preventing the release in the stomach of ingredients which can cause nausea or other undesirable pharmacological effects. The rapid dissolution at higher pH ensures that all of the active ingredient is released in the upper part of the intestine. Hydroxypropyl methylcellulose phthalate and cellulose acetate phthalate are two principal polymers used in enteric coatings.
U.S. Pat. No. 3,391,135 describes a process for preparing low molecular weight cellulose derivatives, wherein 2% by weight of such derivatives should exhibit a solution viscosity of less than 10 cps at 20.degree. C. This reference teaches cellulose acetate, cellulose butyrate, and cellulose phthalate. We have found that cellulose acetate phthalate with a solution viscosity as low as taught in this reference produces unacceptably poor enteric coatings.
U.S. Pat. No. 5,356,634 describes compositions comprised of a cellulose acetate phthalate polymer having phthalyl values from 15 to 25%, an inherent viscosity of about 0.3 to 1.0 dL/g, and a molecular weight of about 15,000 to 75,000, and a cellulose acetate trimellitate polymer having trimellityl values of from 15-27%. The cellulose acetate phthalate polymer described in this reference swells to form a sponge-like non-dissolving matrix for sustained-release applications under the basic conditions of the small intestine and thus by design does not fully dissolve; this feature renders such polymers inappropriate for true enteric coating applications where it is desireable to have the coating dissolve fully under the basic conditions of the small intestine to allow complete and immediate delivery of the drug dosage.
U.S. Pat. No. 4,960,814 describes water dispersible polymeric compositions based on polymers such as cellulose acetate phthalate. Such compositions are generally deficient due to hyrdolytic instability of the phthalate esters.
U.S. Pat. 3,629,237 describes the use of alkali metal salts of oxyacids of halogens to prepare low-viscosity acid phthalates of cellulose ethers. While this reference teaches the inherent viscosity-reduction of cellulose ethers, we have found that alkali metal salts of haloacids such as sodium chlorate are ineffective in reducing the inherent viscosity of many cellulose esters and ethers, while being effective at reducing the inherent viscosity of cellulose acetate phthalate by approximately a factor of 2.7. (See Table VI, below.)
Kirk-Othmer, Encyclopedia of Chemical Technology, Third Edition, Volume 5, pp. 118-143 (1979), John Wiley and Sons, New York, N.Y.; Encyclopedia of Polymer Science and Engineering, Volume 3, pp 158-181 (1985) John Wiley and Sons, New York, N.Y.; and Ullman's Encyclopedia of Industrial Chemistry, Fifth Completely Revised Edition, Volume A5, pp 438-447 (1986) VCH Verlagsgesellschaft, Weinheim, Germany, provide general background information on cellulose ester technology.
Although cellulose acetate phthalate is widely used as the polymer of choice for enteric coatings, the use of cellulose acetate phthalate dissolved in organic solvents has raised some concerns. Increased environmental, health, and safety concerns have forced many manufacturers to reevaluate operations that utilize organic solvents.